ω-3脂肪酸单用及联合表阿霉素对胃癌作用的实验研究

Effect of ω-3 polyunsaturated fatty acid used alone and combined with epirubicin on gastric cancer in vivo

目的:通过动物实验观察ω-3脂肪乳剂单用及联合表阿霉素(EPI)对胃癌移植瘤和荷瘤裸鼠的作用。方法:以胃癌细胞株MGC-803建立的裸鼠动物模型为研究对象,采用ω-3脂肪乳剂单用灌胃及联合表阿霉素腹腔注射的干预手段。荷瘤鼠随机分为对照(A)组、ω-3脂肪乳剂灌胃(B)组、EPI腹腔注射(C)组及ω-3脂肪乳剂联合EPI(D)组。观察荷瘤鼠的一般状况、体重变化、肿瘤生长、转移情况;光镜观察胃癌移植瘤的改变;电镜观察胃癌移植瘤超微结构的改变。结果:①D组肿瘤明显小于A、B组(P<0.05);D组肿瘤的生长速度和大小明显小于C组(P<0.05),A、B组间肿瘤生长无明显差异(P>0.05);与A组相比,B、C、D组未见粘连及淋巴结转移,肿瘤坏死灶较多。②C、D组均出现化疗药物的毒副作用,甚至死亡,但D组状况明显好于C组。③.B组肿瘤组织在电镜下可见肿瘤细胞变性,D组标本中可见到凋亡细胞。结论:①ω-3脂肪酸单独应用可减少胃癌肿瘤的侵袭性和局部转移,导致肿瘤组织局灶性坏死,并能引起肿瘤细胞代谢障碍、凋亡或死亡。②ω-3脂肪酸可增强EPI抗肿瘤效果,说明与EPI单独作用相比,联用ω-3脂肪酸可减少EPI用量。③ω-3脂肪酸可改善化疗动物的一般情况、减少EPI的毒副作用,而对正常器官无不良影响,对机体是安全的。

Objective To evaluate the effect of ω-3 polyunsaturated fatty acid （PUFA） used alone and in combination with epirubicin（EPI） on human gastric carcinoma cell MGC-803 xenografts and on the status of the recipient nude mice. Methods Thirty mice receiving MGC -803 xenografts were randomly assigned to one of the 4 following groups： 7 mice in Group A（control group）; 7 mice in Group B, fed with ω-3 PUFA emulsion; 8 mice in Group C, injected with EPI intra-peritoneally（I/P）; and 8 mice in Group D, fed with ω-3 PUFA emulsion in combination with EPI I/P. The changes in general condition, body weight, tumor growth and metastasis were recorded. Morphology of tumor ceils were observed by optical and electron microscopes. Flow cytometry was used for cell cycle analysis. Results （1）The tumor size in Groups C and D mice was much smaller than those of Groups A and B （P〈0.05）; the tumor size in Group D was much smaller than that of Group C（P〈0.05）. There was no significant difference in tumor growth between Groups A and B（P〉0.05）. Compared with Groups B, C and D, the tumor was appeared to be more invasive in Group A, presenting more tendency to metastasize and few foci of local nacrosis. （2）The side effects of the chemotherapy made their appearence in Groups C and D, but the conditions of Group D mice was better than that of Group C. （3）Under electron microscope, signs of alteration in tumor cell morphology and apoptosis were observed in Groups B and D mice. Conclusions ω-3 PUFA emulsion could not inhibit the growth of MGC-803 xenografts in nude mice, but reduces the tumor invasiveness and of its tendency to metastasize, and induces local tumor necrosis; ω-3 PUFA could also increase the cytotoxicity of EPI on xenografts. Compared with using EPI alone, the combination of the two agents helps to reduce the dosage of EPI, improve the general condition of the nude mice,reduce the side effects of EPI. So, the use of ω-3 PUFA is a relatively safe measure.